Degree of expression of inflammatory proteins in the amniotic cavity, but not prior obstetric history, is associated with the risk severity for spontaneous preterm birth after rescue cerclage for cervical insufficiency

Abstract

ProblemTo examine whether the severity of spontaneous preterm birth (SPTB) risk after rescue cerclage for acute cervical insufficiency (CI) is linked to the degree of inflammatory response in the amniotic fluid (AF) based on the concentrations of various inflammatory proteins and prior obstetric history.Method of studyWe conducted a retrospective cohort study of 65 singleton pregnant women (17–25 weeks) who underwent rescue cerclage following the diagnosis of acute CI and were subjected to amniocentesis. EN‐RAGE, IL‐6, IL‐8, and IP‐10 as inflammatory mediators and kallistatin, MMP‐2/8, and uPA as extracellular matrix remodeling‐related molecules were assayed in the AF using ELISA. The level of each inflammatory mediator was divided into quartiles.ResultsIntra‐amniotic inflammation (IAI; AF IL‐6 level ≥2.6 ng/mL) was independently associated with SPTB after cerclage placement. The odds of SPTB at < 32 weeks, even after adjusting for confounders, increased significantly with each increasing quartile of baseline AF levels for each inflammatory mediator (p for trend < .05). Kaplan‐Meier survival curves showed that the cerclage‐to‐delivery intervals were significantly shorter as the quartiles of AF EN‐RAGE and MMP‐8 increased (log‐rank test, p < .01 each). Neither previous term birth nor prior PTB was associated with SPTB risk or cerclage‐to‐delivery interval after rescue cerclage. Multiparous women who experience CI after term birth showed significantly elevated levels of MMP‐8 and reduced kallistatin levels in the AF.ConclusionIn patients with CI, SPTB risk (especially risk severity) after rescue cerclage is associated with the degree of the inflammatory response in AF as well as the presence of IAI but not with prior obstetric history.

Potential of plasma inflammatory and angiogenic mediators for predicting spontaneous preterm delivery, intraamniotic infection/inflammation, and composite neonatal morbidity/mortality in women with early preterm premature rupture of membranes

“…Although the reasons for this association remain unclear, one possible explanation may be that the local inflammatory/infectious responses in the amniotic cavity (induced by microorganisms or sterile stimuli) may be reflected by changes in the levels of S100A8/A9 and CRP in the maternal circulation. Risk severity of SPTD may be directly related to the degree of inflammatory response in the AF rather than in maternal circulation, as demonstrated in recently reported AF‐based studies in women with PTL, PPROM, and acute cervical insufficiency 6,43,83,84 …”

“…Risk severity of SPTD may be directly related to the degree of inflammatory response in the AF rather than in maternal circulation, as demonstrated in recently reported AF-based studies in women with PTL, PPROM, and acute cervical insufficiency. 6,43,83,84 This study had several limitations. First, MIAC was identified based only on conventional cultivation methods, not including a noncultivation technique (i.e., broad-range 16S rRNA polymerase chain reaction), despite the fact that these two approaches can be used complementarily for MIAC identification.…”